On June 1, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment and immune system to overcome tumor immune evasion and drug resistance, reported positive interim data from its randomized, controlled, open label, multicenter Phase 2 study of CM24 in second-line metastatic pancreatic ductal adenocarcinoma (PDAC) presented at a late-breaking abstract poster presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Purple Biotech, JUN 1, 2024, View Source;id=308199&p=2326565&I=1206939-c7Z3G6f3m8 [SID1234643938]).

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"These exciting interim data demonstrate the potential of CM24 in combination with nivolumab plus the standard-of-care chemotherapy regimen Nal-IRI/5FU/LV to improve clinical outcomes for advanced metastatic PDAC patients. We are highly encouraged by the meaningful results of our primary endpoint, Overall Survival, as well as by the concordant and consistent improvement in all secondary endpoints including PFS, ORR, DCR and CA19-9" stated Gil Efron, Chief Executive Officer of Purple Biotech.

Michael Cecchini, MD Assistant Professor of Medicine at the Yale Cancer Center, a principal investigator in this study, commented, "As a clinician, it is encouraging to see these interim data in the Nal-IRI arm suggesting the potential for improved clinical outcomes for patients with late-stage metastatic PDAC who are in dire need of new effective therapies. These patients face very limited time with their families, and the prospect of potentially lengthening their lives while delaying their disease progression by approximately two months overall is clinically meaningful. These data justify further investigation of CM24 in combination with nivolumab together with standard-of-care chemotherapy to potentially improve outcomes for patients facing a very poor prognosis from this type of tumor".

The Phase 2 study is evaluating CM24, a novel first-in-class multi-functional anti-CEACAM1 antibody, in combination with Bristol Myers Squibb’s immune checkpoint inhibitor nivolumab plus SoC chemotherapy in second-line PDAC patients versus SoC chemotherapy alone. CM24 is a humanized monoclonal antibody that blocks CEACAM1, an immune checkpoint protein responsible for tumor immune evasion and poor tumor response and/or resistance to immune checkpoint inhibitors. The primary endpoint of the study is OS and the secondary endpoints include PFS, ORR and DCR. A Bayesian methodology was used to estimate the magnitude of effect of the experimental arm versus the SoC arm and the study is not powered for hypothesis testing. A total of 63 patients have been enrolled, across 18 centers in the U.S., Spain, and Israel in 2 parallel independent randomized study cohorts (total of 2 arms per cohort). The experimental arms administered patients with CM24 plus nivolumab and a choice of one of two SoC chemotherapies for second-line PDAC, dependent on prior first line therapy regimen; either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil (5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV), while the control arms administered either respective chemotherapy alone. CA19-9 as well as additional exploratory biomarkers are also being evaluated. Of the 63 patients enrolled, 32 were in the gemcitabine/nab-paclitaxel study (experimental and control) and 31 were in the Nal-IRI/5FU/LV study (experimental and control). An analysis of the gemcitabine/nab-paclitaxel study will be performed when the data are sufficiently mature. Topline final data are expected by the end of 2024.

The study interim efficacy results as of the cutoff date of May 8, 2024, are summarized in the following table:

Metric CM24 + Nivolumab + Nal/IRI/5FU/LV Arm
(n = 16) Nal/IRI/5FU/LV Arm
(n = 15)
Hazard ratio for OS 0.74 (95% CI: 0.31-1.77)
Median OS 7.72 months 5.62 months
6 months OS rate 53% 39%
Hazard Ratio for PFS 0.72 (95% CI: 0.33-1.60)
Median PFS 3.8 months 1.9 months
3 months PFS rate 60% 47%
6 months PFS rate 19% 10%
ORR 25% 7%
DCR 63% 40%
A consistent and continuous decrease of CA19-9, a validated and clinically predictive PDAC biomarker, was observed in the experimental arm (61% on average) vs. an increase in the control arm (34% on average).

The CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated, with the most frequent treatment emergent Grade 3 or higher adverse events being diarrhea (19%), fatigue (19%) and anemia (6%).

On June 1, 2024 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported longer follow-up data from the EGFRwt cohort and initial clinical efficacy data from the EGFRmut cohort from the on-going AFM24-102 study in NSCLC (Press release, Affimed, JUN 1, 2024, https://www.affimed.com/affimed-provides-follow-up-data-of-afm24-plus-atezolizumab-showing-durable-responses-in-heavily-pretreated-nsclc-egfr-wild-type-patients-and-positive-initial-data-from-the-nsclc-egfr-mutant-cohort/ [SID1234643937]).

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As of the updated data cutoff on May 13, 2024 for the 17 EGFRwt patients previously reported on, 15 patients were response-evaluable. Four confirmed objective responses were seen: 1 complete response (CR) and 3 partial responses (PR). In addition, 8 patients achieved stable disease (SD), resulting in a disease control rate of 71%. Median progression-free survival was 5.9 months with median follow-up of 7.4 months. Importantly 3 of 4 responses were ongoing for more than 7 months. All responders were resistant to checkpoint inhibitor treatment prior to the study, which supports the hypothesis that combining AFM24 with atezolizumab may provide an alternative strategy to overcome resistance to existing therapies.

As of May 21, 2024, 21 heavily pretreated EGFRmut patients (median of 3 prior therapies) had received the combination therapy of which 13 were response-evaluable. The combination of AFM24 with atezolizumab showed encouraging signals of clinical activity including 1 CR, 3 PRs and 6 patients with SD. As of the data cut-off, all responses were on-going. EGFRmut NSCLC is considered an immunogenically weak subtype where single-agent therapy with immune checkpoint inhibitors have exhibited poor response rates. The data suggests that the combination of AFM24 and atezolizumab could be acting synergistically to improve efficacy outcomes.

AFM24 and atezolizumab combination therapy demonstrated a manageable safety profile. Side effects were consistent with the known safety profiles of these agents. The most frequent side effects observed were mild to moderate infusion related reactions and transient mild to moderate increase in liver enzymes.

"The efficacy of the combination of AFM24 and atezolizumab in these heavily pretreated NSCLC patients is encouraging and supports our hypothesis of a synergistic activity of AFM24 with PD-1/PD-L1 blockade. We believe the durability of the responses in EGFRwt tumors is remarkable and is unlikely driven by PD-1/PD-L1 blockade alone, as all patients with responses had documented progression on their previous PD-1/PD-L1 therapy. In addition, median PFS of atezolizumab, even in checkpoint naïve patients, is only 2.8 months," said Dr. Andreas Harstrick, Chief Medical and acting Chief Executive Officer of Affimed. "This growing body of evidence reinforces our belief that AFM24 in combination with check point targeting can address pressing unmet medical needs in refractory NSCLC patients."

The EGFRwt NSCLC cohort of the study will enroll up to 40 patients and the EGFRmut NSCLC cohort will enroll up to 25 patients. Recruitment in both cohorts is ongoing, and further updates are expected in H2 2024.

Conference Call and Webcast Information

Affimed will host a conference call and webcast for the financial community on June 1, 2024, at 6:00 p.m. CDT / 7:00 p.m. EDT. Dr. Harstrick and Dr. Hye Ryun Kim, Professor at Yonsei University College of Medicine, Seoul, Korea, will review the latest clinical findings and address questions.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link:

https://register.vevent.com/register/BIff607338e5d247f99b548240be2ad413, and you will be provided with dial-in details and a pin number.

About AFM24
AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

On June 1, 2024 Pfizer Inc. (NYSE: PFE) reported detailed overall survival (OS) results from the Phase 3 ECHELON-3 study of ADCETRIS (brentuximab vedotin) in combination with lenalidomide and rituximab for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Seagen, JUN 1, 2024, View Source [SID1234643931]). The study showed that the ADCETRIS combination reduced patients’ risk of death by 37% compared to placebo in combination with lenalidomide and rituximab (HR 0.63 [95% CI: 0.445-0.891] p=0.0085). The overall survival benefit was consistent across levels of CD30 expression.

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The ECHELON-3 results will be presented as a late-breaker (LBA7005) in an oral session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting along with four-year results from the Phase 3 HD21 trial in advanced classical Hodgkin lymphoma (cHL) (LBA7000).

"ECHELON-3 is one of the first randomized, placebo-controlled Phase 3 studies to demonstrate an overall survival benefit in patients with relapsed/refractory DLBCL after two or more prior lines of systemic therapy," said principal investigator Dr. Jeung-A Kim, College of Medicine, The Catholic University of Korea. "The clinically meaningful improvement in survival demonstrates the potential benefit of this ADCETRIS regimen in relapsed/refractory DLBCL, particularly for patients whose disease has progressed after CAR-T therapy or bispecific antibody treatment or individuals who are not able to receive these treatments."

ADCETRIS is approved in the U.S. as monotherapy or in combination with chemotherapy for seven lymphomas including certain types of cHL, anaplastic large cell lymphoma and peripheral T-cell lymphoma. Seven-year survival data for an ADCETRIS regimen for patients with advanced stage cHL will be shared in a poster presentation (7053) at the ASCO (Free ASCO Whitepaper) Meeting on June 3.

"Three Phase 3 trials in three different types of lymphoma have now demonstrated that an ADCETRIS-containing regimen improved overall survival," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "ADCETRIS is a standard of care medicine in its approved indications today, and these impressive results from an interim analysis highlight its potential to benefit people with relapsed/refractory DLBCL regardless of CD30 expression."

DLBCL is the most common lymphoma and is aggressive and difficult to treat, with up to 40 percent of patients experiencing disease progression after initial therapy.1,2

Among 230 randomized patients in the trial, the interim analysis showed that median OS in patients randomized to receive ADCETRIS, lenalidomide and rituximab was 13.8 months (95% CI: 10.3-18.8) compared to 8.5 months (95% CI: 5.4-11.7) in patients randomized to lenalidomide and rituximab plus placebo.

Median progression-free survival (PFS) was 4.2 months (95% CI: 2.9-7.1) in the ADCETRIS arm versus 2.6 months (95% CI: 1.4-3.1) in the lenalidomide and rituximab plus placebo arm (HR 0.527 [95% CI: 0.380-0.729] p<0.0001). The overall response rate for patients treated with the ADCETRIS regimen was 64.3% (95% CI: 54.7-73.1) versus 41.5% (95% CI: 32.5-51.0) in the lenalidomide and rituximab plus placebo arm. The complete response rate was 40.2% in ADCETRIS-treated patients (95% CI: 31.0%, 49.9%) compared to 18.6% (95% CI:12.1%, 26.9%) in the lenalidomide and rituximab plus placebo arm.

The most frequently reported treatment-emergent adverse events (TEAEs) Grade 3 or higher for the ADCETRIS versus placebo arms were: neutropenia (43% vs 28%), thrombocytopenia (25% vs 19%) and anemia (22% vs 21%). Peripheral sensory neuropathy was infrequent and low grade for each arm with Grade 3 events of 4% vs 0%.

About ECHELON-3

ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase 3 study evaluating ADCETRIS plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant or CAR-T therapy. In this global study, 230 patients were randomized across North America, Europe and Asia-Pacific. The primary endpoint is OS in the intent to treat population, with key secondary endpoints of PFS and ORR as assessed by investigator. Other secondary endpoints include complete response rate, duration of response, safety and tolerability.

About Diffuse Large B-cell Lymphoma

DLBCL is the most frequent type of lymphoma and is aggressive and difficult to treat.1,2 More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25 percent of all lymphoma cases.2 DLBCL can develop spontaneously or as a result of diseases such as chronic lymphocytic lymphoma/small lymphocytic lymphoma, follicular lymphoma, or marginal zone lymphoma.1 Up to 40 percent of patients relapse or have refractory disease after frontline treatment.2

About ADCETRIS

More than 55,000 patients have been treated with ADCETRIS in the U.S. since its first U.S. approval in 2011, and more than 140,000 patients have been treated with ADCETRIS globally.

ADCETRIS is an antibody-drug conjugate (ADC) comprised of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS is approved in seven indications in the U.S.:

Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018)
Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (2022)
Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
Adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011)
Adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018)
Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. (2011)
Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) after prior systemic therapy (2017)
Pfizer and Takeda jointly develop ADCETRIS. Under the terms of the collaboration agreement, Pfizer has U.S. and Canadian commercialization rights, and Takeda has rights to commercialize ADCETRIS in the rest of the world. Pfizer and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) for injection U.S. Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML, and death can occur in ADCETRIS-treated patients.

CONTRAINDICATION

Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

WARNINGS AND PRECAUTIONS

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment. Avoid use in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.

Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with pre-existing GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.

Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

L actation: Breastfeeding is not recommended during ADCETRIS treatment.

Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here.

On June 1, 2024 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported the presentation of updated exploratory subgroup analyses from the SIENDO study (NCT03555422), in patients with advanced or recurrent TP53 wild-type endometrial cancer at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Karyopharm, JUN 1, 2024, View Source [SID1234643930]). The data were presented in a special ASCO (Free ASCO Whitepaper) plenary series rapid abstract update session on June 1 at 12:30pm CT and simultaneously published in the Gynecologic Oncology Journal.

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The primary analysis of the Phase 3 SIENDO study of selinexor maintenance therapy in advanced or recurrent endometrial cancer showed improvements in median PFS for the intent-to-treat (ITT) population but were not clinically meaningful. However, an exploratory analysis of a pre-specified subgroup of patients with TP53 wild-type endometrial cancer showed a promising efficacy signal.

In the exploratory subgroup analysis, 113 patients with TP53 wild-type advanced/recurrent endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy after 1L platinum-based chemotherapy. As of the April 1, 2024 data cut-off date, and a median duration of follow-up of 36.9 months, selinexor-treated patients had a median PFS of 28.4 months compared to 5.2 months for patients receiving placebo. In selinexor-treated patients with TP53 wild-type/pMMR and TP53 wild-type/dMMR endometrial cancer, median PFS was 39.5 months and 13.1 months compared to 4.9 months and 3.7 months in those treated with placebo, respectively. Although immature, preliminary overall survival (OS) in the TP53 wild-type subgroup was promising with a hazard ratio of 0.65; median OS for selinexor has not been reached.

The updated analyses also highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess quality and toxicity-adjusted PFS. The findings showed the restricted mean Q-TWiST for selinexor to be 26 months compared to 15 months for placebo, resulting in a difference of nearly 11 months.

"The approximately 40 months median PFS observed with selinexor in patients whose tumors are both TP53 wild-type and pMMR, coupled with the robust QTWiST analysis, suggests that selinexor may be an optimal maintenance therapy in endometrial cancer," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research at Karyopharm. "Our ongoing Phase 3 trial will definitively assess these benefits and may lead to a new standard of care in the novel subgroup of patients defined by TP53 wild-type status."

No new safety signals were identified as of the data cut-off date of April 1, 2024. The most common treatment-emergent adverse events (TEAEs) in selinexor treated TP53 wild-type patients were nausea (90%), vomiting (60%) and diarrhea (45%), the majority of which were grades 1-2. The most common reported grade 3-4 TEAEs included neutropenia (20%), nausea (13%), and thrombocytopenia (10%). TEAEs leading to discontinuations were reported in 17% of patients.

"It is exciting to see the emerging data around progression free survival, as well as an encouraging trend in overall survival and the Q-TWiST metric in the TP53 wild-type subgroup analysis from the SIENDO study," said Vicky Makker, MD, Gynecologic Oncologist, Memorial Sloan Kettering Cancer Center. "The long-term follow-up data further reinforce how selinexor could benefit patients with endometrial cancer, including patients with mismatch repair-proficient disease, and add to the growing body of evidence supporting the potential role of selinexor as a maintenance treatment option for patients whose options are limited."

A copy of the presentation from the "ASCO Plenary Series: Rapid Abstract Updates" special session can be accessed under "Publications and Presentations" in the Investor section of the Company’s website, View Source

Selinexor is being evaluated in a global, Phase 3, randomized, double-blind study, EC-042 (XPORT-EC-042; NCT05611931), as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. Karyopharm expects to report data from this trial in the first half of 2025.

The following Karyopharm abstracts will also be presented at ASCO (Free ASCO Whitepaper):

Abstract Title

Presentation Type

Abstract #

Session Date/Time

Endometrial Cancer

Phase 3 Dose Selection for Selinexor in TP53wt Endometrial Cancer Based on Exposure-Response Analysis

Poster

5594

June 3, 2024

9:00am – 12:00pm CDT

Myelofibrosis

Phase 3 Randomized Double-Blind Study Evaluating Selinexor, an XPO1 inhibitor, Plus Ruxolitinib in Jaki-Naïve Myelofibrosis

Poster

TPS6594

June 3, 2024

9:00am – 12:00pm CDT

Phase 2 Study Evaluating Selinexor Monotherapy in Patients with Jaki-Naïve Myelofibrosis and Moderate Thrombocytopenia

Poster

TPS6593

June 3, 2024

9:00am – 12:00pm CDT

About the EC-042 Study
EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 study was initiated in November 2022 and is expected to enroll up to 220 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The primary endpoint of the study is progression free survival (PFS), as assessed by an investigator, with overall survival as a key secondary endpoint. Further, in connection with the EC-042 Study, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOneCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type.

About the SIENDO Study
Karyopharm’s evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from its ongoing SIENDO Study, a European Network of Gynaecological Oncological Trial Groups (ENGOT)-led trial in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc. The SIENDO Study is a multicenter, randomized, double-blinded Phase 3 study evaluating the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (NCT03555422). Participants in this study with advanced or recurrent disease who had a partial response or a complete response after at least 12 weeks of taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression. The primary endpoint in the study was PFS from time of randomization until death or disease progression as assessed by an investigator, with the goal of the study demonstrating a HR of 0.6. In the first quarter of 2022, Karyopharm presented top-line data from the SIENDO study, including preliminary exploratory subgroup analyses. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo in the full trial population, which was not clinically meaningful. There were no new safety signals identified, and a discontinuation rate of 10.5% due to adverse events (AEs). The most common treatment-emergent AEs in the SIENDO study of any grade were: nausea (84%), vomiting (52%), constipation (37%) and thrombocytopenia (37%). The most common grade 3 treatment-emergent AEs were nausea (10%), neutropenia (9%), thrombocytopenia (7%) and asthenia (6%).

About Endometrial Cancer
Endometrial cancer is the most common cancer of the female reproductive organs in the U.S., with approximately 67,880 new cases expected in 2024 leading to nearly 13,250 deaths.1 In 2022, there were approximately 124,874 new cases and 30,272 deaths in Europe from endometrial cancer, while on a global scale there were 420,368 new cases and approximately 97,723 deaths.2 Since 2000, the incidence of new cases and deaths from endometrial cancer have risen.3 Risk factors include obesity, Type 2 diabetes, high-fat diets, use of tamoxifen and oral estrogens, and delayed menopause.4

About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma who have received at least one prior therapy; (ii) in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and (iii) in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm’s partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.

Please refer to the local Prescribing Information for full details.

Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.

Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

Serious Infection: Monitor for infection and treat promptly.

Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.

The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On June 1, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported three posters about KIMMTRAK (tebentafusp-tebn) for the treatment of patients with unresectable or metastatic uveal melanoma (mUM) at the 2024 ASCO (Free ASCO Whitepaper) (American Society for Clinical Oncology) Annual Meeting (Press release, Immunocore, JUN 1, 2024, View Source [SID1234643929]). These data showed that treatment benefit for patients with stable disease and any confirmed tumor reduction was similar to patients with partial response.

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"In both Phase 2 and Phase 3 KIMMTRAK trials, patients with stable disease and durable tumor reduction, regardless of depth, had similar benefit as patients with RECIST partial response," said Mohammed Dar, Senior Vice President, Clinical Development, and Chief Medical Officer, Immunocore. "The data presented at ASCO (Free ASCO Whitepaper) builds upon the mounting evidence confirming that disease control is the best early radiographic measure of clinical benefit across our ImmTAC platform."

"KIMMTRAK is now the standard of care, in launched countries, for HLA-A*02:01-positive patients with metastatic or unresectable uveal melanoma," said Ralph Torbay, Immunocore’s Chief Commercial Officer. "Physicians can now leverage these data, presented at ASCO (Free ASCO Whitepaper) today, to positively inform their conversations with patients who have stable disease and minor reductions in tumor size."

Of the 127 patients treated with KIMMTRAK in the Phase 2 trial (IMCgp100-102), 25% (32/127) had any tumor reduction that was confirmed in at least one subsequent scan, including 6 partial responses (PR), an overall response rate of 5%, and 20% (26/127) stable disease (SD). The clinical outcomes in the 26 patients with SD were similar to the 6 PR patients, including durable duration of tumor reduction or response, ctDNA molecular response, and overall survival. In the Phase 3 trial (IMCgp100-202), KIMMTRAK-treated patients with SD who had any confirmed tumor reduction had durability of tumor reduction of 11 months, which was the same as the durability of response for patients with RECIST PR or CR.

Full poster details:

Stable disease with confirmed tumor reduction has a similar clinical outcome as RECIST partial response for tebentafusp in metastatic uveal melanoma
Presenting author: Alexandra Ikeguchi

Association between clinical and disease characteristics and detectable or undetectable baseline ctDNA in patients with metastatic uveal melanoma
Presenting author: Paul Nathan

Baseline and serial ctDNA dynamics predicts outcomes in patients treated with first-line tebentafusp including those who were and were not treated beyond progression
Presenting author: Ryan Sullivan